To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines； further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly； replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

Objective: To provide reference for the correct understanding and accurate implementation of the general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition Volume Ⅳ.
Methods: Introduce the main characteristics and content of the additions and revisions of the general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition Volume Ⅳ.
Results: The general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition are more harmonized with the relevant guidelines of the ICH Q series, and the inclusion of advanced and mature instrument analysis technology standards and analysis method standards related to drug safety, efficacy, and quality controllability is further increased.
Conclusion: The general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition have provided a more convenient new bridge for China’s drugs to go international, standardized testing technology support for achieving full process quality control, and better meet the needs of drug research and development, production, quality control, and supervision in China.

It is believed that the occurrence and development of squamous cell carcinoma （SCC） is closely associated with inflammatory responses. The theory of fire and heat， advocated by LIU Wansu， provides significant clinical guidance for understanding the pathogenesis and treatment of SCC. Based on this theory， the pathological mechanisms and clinical characteristics of SCC at different stages were analyzed. In the precancerous and early stages， the primary pathogenesis is qi stagnation leading to internal generation of constrained heat； in post-surgery， the condition shifts to qi deficiency with latent yin fire； during the treatment phase， the pathogenesis involves accumulation of pathogenic factors， excess toxins， and severe heat toxicity； in the late stage， the main pathology is yin deficiency with toxic heat， and phlegm-stasis obstruction of the internal organs. Corresponding stage-based treatment strategies are proposed. In the early stage， regulating qi movement to dissipate constrained heat； for post-surgery， tonifying qi and raising yang to dispel latent fire； during treatment stage， clearing heat and detoxifying to eliminate cancerous toxins； and in the late stage， nourishing yin and unblocking the bowels to clear deficiency heat.

OBJECTIVE To explore the potential mechanism of ketamine-induced cognitive impairment in mice based on metabolomics. METHODS Male C57BL/6 mice were randomly divided into control group and ketamine group （25 mg/kg）， with 12 mice in each group. Each group of mice was intraperitoneally injected with normal saline or corresponding drugs， 4 times a day， for 10 consecutive days. On the last 2 days of drug administration， the cognitive behavior was evaluated by Y maze and novel object recognition test， and the histopathological changes in the prefrontal cortex （PFC） were observed. Ultra-high performance liquid chromatography-tandem mass spectrometry technology was used to analyze the changes of metabolites in PFC， screen for differential metabolites， and perform pathway enrichment analysis. RESULTS Compared with the control group， the morphology of PFC neurons in the ketamine group of mice was inconsistent. There were cavities around the nucleus， and the number of deeply stained cells increased. The mean optical density value of the Nissl staining positive area was significantly reduced， and the alternation rate and discrimination index were significantly reduced （P＜0.05 or P＜0.01）. In the PFC tissue samples of mice of the two groups， there were a total of 114 differential metabolites， including 73 up-regulated and 41 down-regulated metabolites， including glutamine， succinic acid， ketoglutarate， and choline， etc. The differential metabolites mentioned above were mainly enriched in metabolism of alanine， aspartate and glutamate， metabolism of arginine and proline， γ aminobutyric acid synapses， pyrimidine metabolism， cholinergic synapses pathways， etc. CONCLUSIONS Ketamine can induce cognitive impairment in mice. Its neurotoxicity is related to abnormal synaptic transmission and energy metabolism， and neuroimmune regulation disorders.

Gastric cancer （GC） has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present， the treatment plans are optimized mainly in terms of surgery， radiotherapy， and intervention， while the endpoints of clinical trials， such as patients' overall survival， progression-free survival， and disease-free survival， are still unsatisfactory. Therefore， effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s， Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then， the abnormal metabolic network inside tumor cells has gradually entered into researchers' view， and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years， traditional Chinese medicine （TCM） is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore， linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically， while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer （PLGC） in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor （HIF）-1α， cancer-Myc （c-Myc）， apolipoprotein E （APOE） and pyruvate kinase M2 （PKM2） were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized， with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.

Gastric cancer （GC） has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present， the treatment plans are optimized mainly in terms of surgery， radiotherapy， and intervention， while the endpoints of clinical trials， such as patients' overall survival， progression-free survival， and disease-free survival， are still unsatisfactory. Therefore， effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s， Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then， the abnormal metabolic network inside tumor cells has gradually entered into researchers' view， and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years， traditional Chinese medicine （TCM） is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore， linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically， while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer （PLGC） in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor （HIF）-1α， cancer-Myc （c-Myc）， apolipoprotein E （APOE） and pyruvate kinase M2 （PKM2） were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized， with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.

BACKGROUND:Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic,but only a few patients benefit from vascular recanalization in time,so it is urgent to explore new and effective therapy.As one of the critical pathological changes of ischemic stroke,the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke. OBJECTIVE:To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke,as well as the potential therapeutic targets,to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively,and novel strategies for promoting post-stroke rehabilitation. METHODS:The relevant articles published in CNKI,PubMed and Web of Science databases from 2010 to 2022 were retrieved.The search terms were"Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis"in Chinese and English.Finally,78 articles were included after screening and summarized. RESULTS AND CONCLUSION:(1)Astrocytes play an important role in the maintenance of central nervous system homeostasis.After ischemic stroke,astrocytes change from a resting state to an active state.According to the different severities of cerebral ischemic injury,astrocyte activation changes dynamically from swelling and proliferation to glial scar formation.(2)Mature astrocytes are stimulated to restart the cell cycle,then proliferate and migrate to lesions,which is the main source of the glial scar.Neural stem cells in the subventricular zone,neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes.Endothelin-1,aquaporin 4,ciliary neurotrophic factor and connexins are involved in this process.In addition,chondroitin sulfate proteoglycan,as the main component of the extracellular matrix,forms the dense glial scar barrier with proliferated astrocytes,which hinders the polarization and extension of axons.(3)Activation or inhibition of crucial signal molecules involved in astrocyte activation,proliferation,migration and pro-inflammation functions regulate the glial scar formation.Transforming growth factor beta 1/Smad and Janus kinase/signal transducer and activator of transcription 3 are classical pathways related to astrogliosis,while receptor-interacting protein 1 kinase and glycogen synthase kinase 3β are significant molecules regulating the inflammatory response.However,there are relatively few studies on Smad ubiquitination regulatory factor 2 and Interleukin-17 and their downstream signaling pathways in glial scar formation,which are worthy of further exploration.(4)Drugs targeting astrogliosis-related signaling pathways,cell proliferation regulatory proteins and inflammatory factors effectively inhibit the formation of glial scar after cerebral ischemic stroke.Among them,the role of commonly used clinical drugs such as melatonin and valproic acid in regulating glial scar formation has been verified,which makes it possible to use drugs that inhibit glial scar formation to promote the recovery of neurological function in patients with stroke.(5)Considering the protective effects of glial scar in the acute phase,how to choose the appropriate intervention chance of drugs to maintain the protective effect of the glial scar while promoting nerve regeneration and repair in the local microenvironment is the direction of future efforts.

ObjectiveThis study aims to explore the molecular mechanism of endometrial cell senescence during the window of implantation （WOI） in unexplained recurrent spontaneous abortion （URSA） and the intervention effect of Bushen Huoxue method through the integrated research strategy of bioinformatics， machine learning， and animal experiments. MethodThe microarray gene sets of the endometrium of healthy women of childbearing age and patients with URSA during WOI were retrieved through the gene expression omnibus （GEO） database. The differentially expressed genes （DEGs） of URSA were screened by using the limma package of R language. Weighted gene co-expression network analysis （WGCNA） was used to obtain the most relevant module genes of URSA， and the gene ontology （GO） enrichment analysis and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis were performed. Gene sets related to cell senescence were obtained by the Human Gene Database （GeneCards） and Online Mendelian Inheritance in Man （OMIM）. The Venn online mapping software was used to screen the intersection genes of DEGs of URSA， the most relevant module genes， and the genes related to cell senescence. Then， the search tool for the retrieval of interacting genes/proteins （STRING） was used to analyze the protein-protein interaction （PPI） network of the interacting genes， and the hub genes were screened through Cytohubba. In addition， the least absolute selection and shrinkage operator （LASSO） and random forest algorithm were used to screen diagnostic genes related to cell senescence of URSA. Finally， mouse models with URSA were established and randomly divided into the model group， Bushen Huoxue group， and aspirin group， with six mice in each group， and six normal pregnant mice were selected as a blank group. The Bushen Huoxue group was given Shoutai pill combined with Danggui powder formula granular liquid （12.35 g·kg^-1） by gavage， and the aspirin group was gavaged with aspirin at a dose of 0.011 mL·g^-1. The blank group and model group were given the same volume of distilled water by gavage. Drug administration began on the first day after the discovery of vaginal thrombus （recorded as the first day of gestation， i.e. GD1）， and the mice were sacrificed 12 hours after administration at GD5. The endometrium samples were collected. Quantitative real-time polymerase chain reaction （Real-time PCR） and immunofluorescence were used to detect the expression of cell senescence-related diagnostic genes in the endometrium tissue of URSA mice during WOI and the intervention effect of the Bushen Huoxue method. ResultThe gene set of the GSE165004 microarray was included for bioinformatics analysis. According to the “limma” package of R language， 585 DEGs of URSA were selected （P<0.05）. WGCNA results suggested that the gene in the magenta module was the most closely related to URSA （r=0.32， P<0.05）. The results of the KEGG analysis of the magenta module suggested that the genes were mainly enriched in cell senescence， Hippo， and NF-κB signaling pathways （P<0.05）. In addition， 2 138 genes related to cell senescence were obtained from Genecards and OMIM websites. The Venn online mapping tool was used to obtain 27 intersecting genes of DEGs of URSA， the magenta module genes， and cell senescence-related genes， namely， cell senescence-related DEGs in endometrium tissue during WOI of URSA. PPI analysis showed that synuclein alpha （SNCA）， heme oxygenase 1 （HOMX1）， and matrix metallopeptidase 1 （MMP1） were hub genes. Besides， four diagnostic genes were identified by LASSO regression and random forest， including gelsolin （GSN）， cyclin2 （CCND2）， RB binding protein 8 （RBBP8）， and lysophosphatidic acid receptor 1 （LPAR1）. Animal experiments confirmed that the mRNA level and fluorescence intensity of GSN were significantly increased （P<0.05）， while the mRNA and fluorescence intensity of CCND2， LPAR1， and RBBP8 were significantly decreased （P<0.05） in the model group when compared with the blank group. The expression level of GSN was decreased （P<0.05）， while the expression levels of CCND2， LPAR1， and RBBP8 were remarkably increased （P<0.05） in the Bushen Huoxue group when compared with the model group. ConclusionThe senescence of endometrial cells during WOI of URSA is related to multiple genes. Bushen Huoxue method can act on multiple targets that are related to cell senescence， which may be the key mechanism of improving endometrial receptivity in URSA.

Objective We aimed to investigate the hemostatic effect and mechanism of modified Sijunzi Decoction(MSJZT),consisting of tangshen,India bread,largehead atractylodes rhizome,liquorice root,milkvetch root,ass hide glue,and India madder root,on the zebrafish intestinal bleeding model through 5-hydroxytryptamine(5-HT)and its receptors(5-HT2aR,5-HT2bR).Methods Zebrafish at 4 days post fertilization were used as the research object.An intestinal bleeding model was established by induction with 6 μmol/L simvastatin for 24 hours.The zebrafish were divided into normal group,model group,MSJZT low-,mid-and high-concentration groups(55.6,167,500 mg/L),and after modeling,the corresponding concentration of MSJZT was administered.The samples were collected after 24 hours.Platelet count(PLT)and bleeding status were observed.The content of 5-HT and Caspase 3/7 activity were detected by colorimetry.The gene expressions of 5-HT2aR,5-HT2bR and serotonin transporter(SERT)were detected by real-time PCR.The protein expressions of protein kinase B(AKT),phosphorylated AKT(p-AKT),extracellular signal-regulated protein kinase(ERK),and phosphorylated ERK(p-ERK)were detected by Western blotting.Results The intestinal bleeding rate in the model group was 70.0%,and that in the MSJZT low-,mid-and high-concentration groups was 36.7%,40.0%,and 80.0%,respectively;the intestinal hemostatic effect was 54%,52%,and 7%,respectively.Compared with the model group,the PLT in the MSJZT low-and mid-concentration groups decreased;the content of 5-HT in all MSJZT groups increased,and the gene expressions of 5-HT2aR and 5-HT2bR were up-regulated.The gene expression of SERT was up-regulated in the low-and mid-concentration groups;the Caspase 3/7 activity in the mid-and high-concentration groups was reduced;the expressions of p-AKT and p-ERK proteins were up-regulated in the low-and mid-concentration groups(all P<0.05).Conclusion MSJZT can reduce the incidence and severity of intestinal bleeding in zebrafish intestinal bleeding models.The mechanism may be achieved by activating AKT and ERK signaling pathways through 5-HT and its receptors.

Objective:To compare the characteristics of cerebrospinal fluid (CSF) oligoclonal band electrophoresis examination results between patients with multiple sclerosis (MS) and Guillain-Barré syndrome (GBS), and to provide a basis for the differential diagnosis of the two types of neurological demyelinating diseases.Methods:Case analysis.The retrospective study method was used, and the patients who visited Beijing Tiantan Hospital, Capital Medical University from January 2020 to August 2023 were selected as the research subjects, including 70 MS patients[19 males and 51 females, aged 34 (28, 44) years] and 70 GBS patients [44 males and 26 females, aged 50 (36, 61) years]. The oligoclonal band electrophoresis and immunoglobulin G(IgG) index (IgG I) were performed on the clinical specimens from MS and GBS patients, and CSF routine, CSF biochemistry (glucose, chloride, protein), lactate, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), rubella virus (RV), toxoplasma gondii (TOX), Epstein-Barr virus (EBV), and coxsackievirus were detected simultaneously. The enumeration data were treated with the chi-square test. The measurement data didn′t accord with normal distribution, and were treated with the Mann-Whitney U test. Results:The positive rate of oligoclonal band (OCB) electrophoresis in MS and GBS patients were 80.00% (56/70) and 4.29% (3/70), respectively. The positive rate in MS patients was significantly higher than that in GBS patients (χ 2=82.289, P<0.001). The white blood cells count [5.50 (3.00, 11.00)/μl] and the level of chlorine [127 (125, 128) mmol/L] in CSF of MS patients was higher than that of GBS patients [3.50(2.00, 7.00)/μl, 126(124, 128) mmol/L] ( U=-2.245, P<0.05; U=-2.028, P<0.05), while the levels of CSF protein [33.40(27.61, 39.17)mg/L], glucose [3.59(3.36, 3.88) mmol/L], and lactate [1.55(1.40, 1.73) mmol/L] of MS patients were lower than those of GBS patients [6.71(43.78, 138.30) mg/L, 3.97(3.55, 4.54) mmol/L, 1.80(1.60, 2.00) mmol/L]( U=-6.747, P<0.001; U=-3.651, P<0.001; U=-4.531, P<0.001). The levels of IL-6 [3.36(2.34, 5.02) pg/ml], IL-8 [55.40(46.75, 66.40) pg/ml], and TNF-α [5.63(4.25, 6.63) pg/ml] in CSF of MS patients were lower than those of GBS patients [6.12(3.61, 11.73) pg/ml, 120.00(74.90, 187.80) pg/ml, 6.57(5.25, 8.03) pg/ml]( U=-3.463, P<0.05; U=-5.225, P<0.001; U=-2.785, P<0.05). The positive rates of CMV IgG, TOX IgG, and EBVCA IgG in CSF of MS patients were 36.36% (24/66), 0 and 0, respectively,and the positive rates of those of GBS patients were 85.71% (54/63), 30.16% (19/63), and 19.05% (12/63), respectively. The positive rates of CMV IgG, TOX IgG, and EBVCA IgG in CSF of MS patients were significantly lower than those of GBS patients (χ 2=32.839, P<0.001; χ 2=23.343, P<0.001; χ 2=13.861, P<0.001). Conclusions:The MS patients mainly showed the higher positive rates of OCB. The GBS patients showed elevated CSF protein levels but no significant increase in white blood cell count, namely albuminocytologic dissociation in CSF. Meanwhile, the GBS patients showed elevated levels of intrathecal immunity and inflammation indicators, and a higher positive rate of pathogen antibodies.